ADHD is a prevalent life-span condition, characterized by symptoms of inattention and overactivityimpulsivity. A striking feature of ADHD is the highly context-dependent nature of performance deficits and expression of symptoms. In certain situations, individuals with ADHD seem perfectly able to perform well (eg when the task at hand is stimulating enough), while in other situations, they can’ sit still and are unable to sustain attention (eg when the task is not stimulating enough). Three decades of research have provided support that this may be due arousal regulation deficits. Efficient performance requires maintaining an optimal arousal level regardless of changing contextual factors, and individuals with ADHD easily get into a non-optimal arousal state. The neurobiological underpinnings of this deficit are however not known. Locus coeruleus (LC) dysfunction has been proposed, as the LC, located in the brainstem is crucial for arousal regulation. Investigating the LC in humans poses considerable methodological challenges. However, recent progress made in the development and validation of noninvasive indirect measures (P3 and pupil size) and novel fMRI methods for investigating the LC has provided new exciting opportunities, which we will take advantage of, to, for the first time, investigate the role of the LC in arousal regulation deficits in ADHD. The findings will markedly further our insights into arousal regulation deficits in ADHD and may lead to better treatment.